DDE and PCBs are highly persistent, lipophilic environmental chemicals. They are known to have estrogenic properties and to be carcinogenic in animals. To test the hypothesis that these compounds might play an etiologic role in human breast cancer, a preliminary case-control study was conducted. Elevated levels of DDE and PCBs were found in serum of women with breast cancer compared with non-cancer controls. (Among the 58 cases, cancer had been diagnosed within 6 months of blood donation.) Now, to investigate more broadly the possible role of organochlorines in human carcinogenesis, a series of three "nested" case-control studies is proposed--for breast cancer, colon cancer, and endometrial cancer--among a large population of women who participated in a prospective study of cancer undertaken in New York City during 1985-1992. For breast cancer, there are 240 cases available that occurred at least 12 months after enrollment; for colon cancer, 60-70 cases; for endometrial (uterine) cancer, 35-45 cases. Controls will be individually matched (3:1) on the basis of age, date of enrollment, and either menopausal status or phase of the menstrual cycle. Concentrations of PCBs and DDE will be measured in serum specimens that were obtained at the time of enrollment and stored frozen. The evaluation of associations between DDE, PCBs and cancer will control for potential confounders and effect modifiers, including diet and reproductive history. For breast cancer, repeated blood specimens were taken in later years; these will be analyzed to chart any changes in serum levels that may occur during onset of disease. Several advantages are gained from the use of this study population. Serum specimens have already been obtained; high-quality baseline historical information on dietary and other potential risk factors is in hand; steroid hormone levels are known; and mechanisms for population followup are well established. Data from this study may illuminate the association of environmental toxins, dietary fat and hormones with occurrence of cancer, providing greater understanding of these diseases and opportunities for intervention.